Title:Research on Clinical Decision Making in Life-Threatening Illness (R01)

Announcement Type
This is a reissue of PA-02-118 which was previously released on June 27, 2002.

Update: The following update relating to this announcement has been issued:

November 20, 2006 - The R01 portion of this funding opportunity has been replaced by PA-07-062, which now uses the electronic SF424 (R&R) application for February 5, 2007 submission dates and beyond.

Looking Ahead: As part of the Department of Health and Human Services' implementation of e-Government, during FY 2006 the NIH will gradually transition each research mechanism to electronic submission through Grants.gov and the use of the SF 424 Research and Related (R&R) forms. Therefore, once the transition is made for a specific grant mechanism, investigators and institutions will be required to submit applications electronically using Grants.gov.. For more information and an initial timeline, see http://era.nih.gov/ElectronicReceipt/. NIH will announce each grant mechanism change in the NIH Guide to Grants and Contracts (http://grants.nih.gov/grants/guide/index.html). Specific funding opportunity announcements will also clearly indicate if Grants.gov submission and the use of the SF424 (R&R) is required. Investigators should consult the NIH Forms and Applications Web site (http://grants.nih.gov/grants/forms.htm) for the most current information when preparing a grant application.

This funding announcement seeks to stimulate research on the decision-making processes made by persons faced with life-threatening illness. These illnesses are ones that almost always lead to death in a fairly short period of time if left untreated, but may be chronic – or even cured – if dealt with early in the disease process. An example of a life-threatening illness that may be chronic for some years would be HIV infection when treated. An example of a life-threatening illness that may be cured in its early stages would be breast cancer. Decision-making can occur from the point of adopting preventive behaviors through the end of life. Examples of such decisions could include participating in an HIV vaccine clinical trial, testing for genetic disorder, choosing a treatment intervention vs. watchful waiting (as in early stage prostate cancer), choosing a treatment intervention among several options, joining a therapeutic clinical trial, or making end-of-life care decisions.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.

This announcement will use the R01 mechanism.

Eligible organizations include For-profit organizations, Non-profit organizations, Public or private institutions, such as universities, colleges, hospitals, and laboratories, Units of State government, Units of local government, Eligible agencies of the Federal government, Domestic or foreign institutions/organizations, units of State/Local Tribal governments, Faith-based or community-based organizations

Eligible principal investigators includes any individual with the skills, knowledge, and resources necessary to carry out the proposed research. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

Applicants may submit more than one application, provided they are scientifically distinct.

The National Institute of Nursing Research (NINR) and the National Cancer Institute (NCI) invites research grant applications on clinical decision-making with regard to life-threatening illness. This initiative updates a previous Program Announcement published in 1994 entitled "Research on Clinical Bioethical Dilemmas," and re-issued in 2002 as “Research in Clinical Decision-Making.” The focus of the current announcement is the decision-making process with regard to illnesses that almost always lead to death in a fairly short period of time if left untreated, but may be chronic – or even cured – if dealt with early in the disease process. The underlying disease processes were almost uniformly fatal until very recent advances in biomedical science (e.g. highly active anti-retroviral therapy), or improved screening. An example of a life-threatening illness that may be chronic for many years before development of fatal complications would be HIV infection when treated. An example of a life-threatening illness that may be curable would be early stage breast cancer.

Despite recent advances, the decisions to be made are usually fraught with uncertainty. This program announcement seeks research on how patients (and, where appropriate, patients and families/support systems) cope with uncertainty and arrive at decisions. These decisions may occur at all points along the disease continuum – from pre-disease (i.e., prevention among at risk individuals) to treatment to end of life. Examples of such decisions could include participating in an HIV vaccine clinical trial, testing for genetic disorder, choosing a treatment intervention vs. watchful waiting (as in early stage prostate cancer), choosing a treatment intervention among several options, joining a therapeutic clinical trial, or making end-of-life care decisions.

As before, this announcement seeks out research to build on knowledge needed for patients to become increasingly involved in the clinical decision-making process. At the same time, this announcement is meant to stimulate research on decision-making styles that involve not only the individual, but also other participants, such as family, non-familial caregiver networks, health care providers, clergy, or others. Outcomes, however, must be focused on the patient, or where appropriate the patient/caregiver dyad, or patient/support network nexus.

BACKGROUND

Clinical decision-making is a complex process that requires research into how decisions are made from both intrinsic (individual) and social (interactive) perspectives. Decision-making becomes even more complex when the clinical condition at issue is life-threatening. Such decision-making often occurs in the context of multiple options, including but not limited to selecting screening techniques, preventive treatments, treatments of varying risks and benefits, and the choice of inaction. The decisions that health care providers make may be different than those of the patients and family, suggesting the need for study of mutual decision-making process. Some patients at risk for or having life-threatening illness want to be actively involved in clinical decision-making, while others do not. Still other patients may seem to be passive, but are really engaged in an interactive process with family members or others (e.g. clergy). These processes are not well understood by providers, and therefore require additional research.

One factor that may have an impact upon clinical decisions is the ability of the patient to manage uncertainty. Evidence shows that some cancer patients who have received psychoeducational interventions to manage uncertainty patients are better able to make treatment choices than those who do not receive such training (Germino et al., 1998, Mishel et al. 2002, Mishel et al. 2003). Sometimes prevention or treatment intervention activities can lead to further uncertainty. For example, knowledge of a genetic predisposition to disease may allow for preventive measures, or for early intervention. In some instances, though, it may simply mean knowledge of a possible or likely threat to life that has no effective treatment as yet.

One of the many important decisions that a patient at risk for or having a life-threatening illness may make is whether or not to join a clinical trial. Yet, many patients do not understand what is involved in a clinical trial. Some might avoid participation because they believe that they may be offered a dangerous experimental drug vs. no treatment, rather than understanding the requirement that a large-scale trial of efficacy tests the experimental treatment against a standard treatment. Others have an inflated sense of optimism, not understanding that a Phase 1 trial may offer no survival benefit to the cohort in which it is tested (Sankar 2004). Some research demonstrates that when analyzing the situation presented by the opportunity to enroll in a clinical trial, potential subjects consider a variety of contingencies (Mueller 2004). Understanding these contingencies may provide an entry into developing better modes of communication or other strategies to improve the decision-making process in life-threatening illness.

Some clinical trials are meant to test prevention interventions or vaccines. Recent studies of willingness to participate in HIV vaccine prevention trials (McGrath et al. 2001, O’Connell et al. 2002; Scott et al. 2001) have detected varied interest depending upon the risk status of the target population. This is an area that could benefit from research either in the US or abroad.

Substitute or proxy decision-making occurs on behalf of people who are incapable of making decisions for themselves, including children (e.g., Hinds 2004), the severely mentally ill, and other groups with cognitive deficits. Persons nearing the end of life can also lack the cognitive capacity to understand the impact of clinical decisions. Health care professionals and caregivers can differ in their decisions from each other, and perhaps from what the patient with a life-threatening illness would prefer if given the opportunity.

At other times, neither health care providers, families nor patients perceive the clinical situation as one involving clear decisions based on a desirable outcome. Some have critiqued the entire construct of choice and individual decision-making in the end-of life setting (Drought and Koenig 2002). One of the most difficult decisions to be made at the end of life is whether or not to discontinue life-sustaining treatment. Despite widespread support of advance care planning, less than twenty percent of patients complete an advance directive. However, even the presence of a living will or advance directive may not avoid painful decisional conflict. This is an area ripe for research at both patient and family levels.

Potential Research Areas:

The goal of this program announcement is to increase scientific knowledge in the area of clinical decision-making among persons faced with life-threatening illness in order to develop an evidence base to help patients, families and significant others in the decision-making process. Listed below are examples of areas of clinical decision-making research that would be responsive to this program announcement. They are not listed in any priority order and are not intended to be exhaustive or restrictive. These examples are only illustrative, and applicants are encouraged to propose other topics consistent with the goals of this program. Ultimately, this research should have an impact upon patient outcomes, and not be targeted directly or solely at health providers or the health system.

Determine the manner in which person-level factors, such as gender and racial/cultural identity influence clinical decision-making among persons faced with life-threatening illness.

Identify and test different communication approaches (e.g., technology-based, face-to-face, print, video) to promote understanding by the patient of the clinical decision-making process. Strategies could be targeted to patients with developmental or cognitive limitations.

Investigate the factors influencing the decision-making process to undertake testing for serious genetic disorders among patients and their families. Studies of decision-making around next steps after receiving results, in particular where there is no curative therapy as yet, are also welcome.

Examine issues such as whether advance care planning protects the patient's autonomy and if the health care provided to the patient is altered by advance care planning.

Evaluate different approaches to end of life decision-making besides advanced directives.

Test interventions to assist patients and families in clinical decisions near the end-of-life. Such interventions may assess whether familial conflict is lessened, and include outcomes targeted to bereaved family members.

Section II. Award Information

1. Mechanism(s) of Support

T his funding opportunity will use the R01 award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise follow the instructions for non-modular research grant applications.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

The number and size of the awards will depend on the number of applications received, their relative scientific merit, and the general availability of funds for investigator-initiated research at the participating ICs.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

For-profit organizations

Non-profit organizations

Public or private institutions, such as universities, colleges, hospitals, and laboratories

Units of State government

Units of Local government

Eligible agencies of the Federal government

Domestic Institutions

Foreign Institutions

Units of State Tribal government

Units of Local Tribal government

Faith-based or community-based organizations

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

2. Cost Sharing or Matching
Not required.

3. Other-Special Eligibility Criteria
There is no limit to the number of applications an applicant may submit under this announcement.

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form. The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Charge back of customs and import fees is not allowed.

Format: every effort should be made to comply with the format specifications, which are based upon a standard US paper size of 8.5" x 11."

Applications must be prepared using the research grant application forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to:

Upon receipt applications will be evaluated for completeness by CSR. Incomplete applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.

Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year.

Applicants requesting $500,000 or more in direct costs for any year must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study;

2) Obtain agreement from the IC staff that the IC will accept your application for consideration for award; and,

3) Include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended or revised version of these grant application types. Additional information on this policy is available in the NIH Guide for Grants and Contracts, October 19, 2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. Criteria
Only the review criteria below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established PHS referral guidelines.

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.

Receive a written critique

Receive a second level of review by the appropriate national advisory council or board.

The following will be considered in making funding decisions:

Scientific merit of the proposed project as determined by peer review

Availability of funds

Relevance of program priorities

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not Applicable

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 14 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002 . The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.